For 20 years, the Alpha-1 Antitrypsin Deficiency (AATD) Registry in Ireland, has been helping patients and researchers better understand this rare genetic condition that can damage the lungs and the liver. Now, drawing on this long-term collaboration, RCSI researchers and Alpha-1 Foundation Ireland have uncovered new insights into how the immune system behaves in people both with and without AATD.
The immune system is a complex orchestra of cells and proteins that work tirelessly to protect the body from infections and to heal injuries and damage. AAT is one of these immune system proteins. It is particularly well known for its ability to protect the lungs and to calm damaging inflammation.
People with the condition AATD do not have enough of the AAT protein to protect their lungs, which leads to respiratory damage. The risk and severity of lung disease can be reduced through lifestyle and medical interventions, but early detection is critical.
Since 2004, RCSI and Beaumont Hospital have operated the National AATD Targeted Detection Programme. By working with people who present with lung and liver damage and with their families, more than 500 people in Ireland have been diagnosed with severe AATD, and another 6,000 with moderate AATD. This year, the registry that underpins the programme marks its 20th anniversary – a milestone highlighting RCSI’s sustained support for patient-centred research.
Emerging patterns
The information in the registry powers research into AAT and AATD, including the latest study which is the first to examine seasonal variation in AAT levels at a population scale.
After analysing 20,000 patient records, the researchers found that in healthy men, levels of AAT in blood vary throughout the year. This pattern was not seen in women, who generally had higher AAT levels all year round. These differences in AAT levels between men and women also varied by age, appearing after puberty and diminishing around menopause, suggesting that sex hormones are involved in or control the production of AAT.
In people with AATD, the picture was reversed. Those with moderate forms of the condition displayed less seasonal fluctuation, while individuals with severe AATD showed no seasonal variation at all – and in this group, men had relatively higher levels than women. The age-specific variations in AAT levels were also lost in people with severe AATD.
These results suggest that hormonal signalling may be disrupted in AATD, providing clues into how the condition develops and raising questions about the importance of AAT in fertility and pregnancy.
Tailored treatments
The study, funded by the Health Service Executive and the US Alpha-1 Foundation, opens the door to future research into how AATD progresses and how treatments might be better tailored.
Together with the National AATD Targeted Detection Programme, this work reflects RCSI’s commitment to advancing understanding of rare genetic conditions and improving patient outcomes.
The paper Seasonal Changes in Circulating Alpha-1 Antitrypsin are Altered by Sex and Genetic Deficiency is published in the American Journal of Respiratory and Critical Care Medicine.
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